AUTHOR=Perišić Nanut Milica , Sabotič Jerica , Jewett Anahid , Kos Janko 

TITLE=Cysteine Cathepsins as Regulators of the Cytotoxicity of NK and T Cells

JOURNAL=Frontiers in Immunology

VOLUME=Volume 5 - 2014

YEAR=2014

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2014.00616

DOI=10.3389/fimmu.2014.00616

ISSN=1664-3224

ABSTRACT=Cysteine cathepsins are lysosomal peptidases involved at different levels in the processes of the innate and adaptive immune responses. Some, such as cathepsins B, L and H are expressed constitutively in most immune cells. In cells of innate immunity they play a role in cell adhesion and phagocytosis. Other cysteine cathepsins are expressed more specifically. Cathepsin X promotes dendritic cell maturation, adhesion of macrophages and migration of T cells. Cathepsin S is implicated in major histocompatibility complex class II antigen presentation, whereas cathepsin C, expressed in cytotoxic lymphocytes (CTLs) and natural killer (NK) cells, is involved in processing progranzymes into proteolytically active forms, which trigger cell death in their target cells. The activity of cysteine cathepsins is controlled by endogenous cystatins, cysteine protease inhibitors. Of these, cystatin F is the only cystatin that is localized in endosomal/lysosomal vesicles. After proteolytic removal of its N terminal peptide, cystatin F becomes a potent inhibitor of cathepsin C with the potential to regulate progranzyme processing and cell cytotoxicity. This review is focused on the role of cysteine cathepsins and their inhibitors in the molecular mechanisms leading to the cytotoxic activity of T lymphocytes and NK cells in order to address new possibilities for regulation of their function in pathological processes.